The regulation of miRNAs by reconstituted high-density lipoproteins in diabetes-impaired angiogenesis

Diabetic vascular complications are associated with impaired ischaemia-driven angiogenesis. We recently found that reconstituted high-density lipoproteins (rHDL) rescue diabetes-impaired angiogenesis. microRNAs (miRNAs) regulate angiogenesis and are transported within HDL to sites of injury/repair. The role of miRNAs in the rescue of diabetes-impaired angiogenesis by rHDL is unknown. Using a miRNA array, we found that rHDL inhibits hsa-miR-181c-5p expression in vitro and using a hsa-miR-181c-5p mimic and antimiR identify a novel anti-angiogenic role for miR-181c-5p. miRNA expression was tracked over time post-hindlimb ischaemic induction in diabetic mice. Early post-ischaemia when angiogenesis is important, rHDL suppressed hindlimb mmu-miR-181c-5p. mmu-miR-181c-5p was not detected in the plasma or within HDL, suggesting rHDL specifically targets mmu-miR-181c-5p at the ischaemic site. Three known angiogenic miRNAs (mmu-miR-223-3p, mmu-miR-27b-3p, mmu-miR-92a-3p) were elevated in the HDL fraction of diabetic rHDL-infused mice early post-ischaemia. This was accompanied by a decrease in plasma levels. Only mmu-miR-223-3p levels were elevated in the hindlimb 3 days post-ischaemia, indicating that rHDL regulates mmu-miR-223-3p in a time-dependent and site-specific manner. The early regulation of miRNAs, particularly miR-181c-5p, may underpin the rescue of diabetes-impaired angiogenesis by rHDL and has implications for the treatment of diabetes-related vascular complications

CHANGES IN NUTRITIONAL STATUS AND DIETARY INTAKE DURING AND AFTER HEAD AND NECK CANCER TREATMENT

Background. The purpose of this study was to test whether nutritional status of patients with head and neck cancer changes during and after treatment. Methods. Nutritional status (including body weight, lean mass, and fat mass) and dietary intake were assessed in 29 patients with head and neck cancer. Patients were assessed 1 week before, and 1 and 4 months after treatment (radiotherapy, either alone or combined with chemotherapy or surgery). Results. During treatment, body weight (-3.6 +/- 5.3 kg; p = .019) and lean mass (-2.43 +/- 2.81 kg; p = .001) significantly declined. Patients with sufficient intake (>= 35 kcal and >= 1.5 grams protein/kg body weight) lost less body weight and lean mass than patients with insufficient intake (mean difference, -4.0 +/- 1.9 kg; p = 0.048 and -2.1 +/- 1.0 kg; p = .054, respectively). After treatment, only patients with sufficient intake gained body weight (2.3 +/- 2.3 kg) and lean mass (1.2 +/- 1.3 kg). Conclusion. Patients with head and neck cancer fail to maintain or improve nutritional status during treatment, despite sufficient intake. (C) 2010 Wiley Periodicals, Inc. Head Neck 33: 863-870, 201